tbuckley/cabot-search huggingface dataset:
Abstract 12367: Tavr Outcomes in Overweight and Obese Patients: Systematic Review and Meta-Analysis
Authors: Rahul Gupta, Amir Hossein Behnoush, Amirmohammad Khalaji, Elham Mahmoudi, Theresa Maitz, Akshay Goel, Aaqib H Malik, Dhrubajyoti Bandyopadhyay, Wilbert S Aronow, Apurva Vyas, Nainesh Patel
Journal: Circulation (2022)

Introduction: In recent years, the “obesity paradox” has been shown in studies demonstrating better outcomes in overweight and obese patients undergoing percutaneous or surgical cardiovascular procedures. This study compares the effect of body-mass index (BMI) on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). Methods: A comprehensive systematic search was conducted in PubMed, Web of Science, and Cochrane library for relevant studies. Studies were included if they had categories for BMI (normal-weight, overweight, and obese) and reported the outcomes of TAVR in each group. Random-effects using STATA was performed for the meta-analysis. Results: 34 studies with 96,093 patients were included in our study. Overweight and obese patients had a significantly lower rate of 1-year all-cause mortality, long-term all-cause mortality and moderate to severe aortic regurgitation compared to normal-weight patients (Figure 1). Incidence of 30-day myocardial infarction was lower in overweight patients, and 1-year stroke incidence was significantly lower in obese patients compared with normal cases. In contrast, permanent pacemaker implantation was more observed in overweight and obese patients. There was no significant difference in outcomes in underweight patients compared to normal-weight ones except for a higher rate of major vascular complications in underweight cases. Conclusions: Our analysis showed improved outcomes in terms of all-cause mortality and aortic regurgitation in overweight and obese patients undergoing TAVR compared to normal-weight patients.
Abstract 11693: Improving Angiotensin Receptor-Neprilysin Inhibitor Utilization for Veterans Admitted With Acute Decompensated Heart Failure: A Single-Center Experience
Authors: Daniel L Underberg, Michael Jiang, SEAN DUNNE, Anjan Tibrewala, Mayank Kansal
Journal: Circulation (2022)

Objective: Improve angiotensin receptor-neprilysin inhibitor (ARNI) utilization among patients admitted with acute decompensated heart failure (HF) through a multidisciplinary quality improvement (QI) intervention. Background: ARNIs reduce mortality and hospitalizations for patients with HF and abnormal systolic function; current guidelines recommend them as first-line agents for Stage C HF. Inpatient initiation of ARNIs during an acute exacerbation is cost-effective and safe. Despite this, ARNI utilization remains low nationally and at our center. Methods: We implemented a multidisciplinary QI intervention at a large urban Veterans Affairs (VA) medical center. The intervention included electronic health record system redesign to provide clinical decision support, a new pharmacy-led screening process and recommendation system to the primary inpatient team, and an educational campaign. Our primary outcome metric was monthly ARNI initiation rate, defined as the number of new ARNI initiations divided by the number of eligible patients admitted for an acute HF exacerbation. We used a statistical process control (XmR) chart to measure change. Results: We observed a statistically significant, non-random improvement in mean monthly ARNI initiation rate from 8.4% pre-intervention to 35.7% post-intervention. An XmR chart is shown in Figure 1. Split limits analysis showed variation post-intervention was within statistical control, suggesting sustainable change. Conclusions: Our outcomes demonstrate successful implementation of a multidisciplinary intervention to improve ARNI utilization among patients admitted with acute decompensated HF at a large VA medical center. ARNI initiation rate increased significantly post-intervention, and the split limits analysis suggests that our results represent sustainable change. A longer period of data collection will be useful to assess HF readmission and mortality rates in response to this intervention.
Abstract 12256: Symptomatic Supratherapeutic International Normalized Ratio on Rivaroxaban: A Case Report and a Systematic Review
Authors: Angela Khidhir
Journal: Circulation (2022)

Rivaroxaban is a direct oral anticoagulant that works by inhibiting factor Xa. Direct anticoagulants have largely replaced direct vitamin K inhibitors (VKAs) due to the increased risk of major hemorrhages and the need for regular monitoring and dose adjustments. However, there have been multiple reports of elevated international normalized ratio (INR) and incidents of bleeding in patients on rivaroxaban, which brings into question the potential need for monitoring. The purpose of this review is to differentiate the patients that may benefit from regular monitoring and to propose future directions for implementation of monitoring. Here we report a case of an INR of 4.8 in a patient who presented with a gastrointestinal bleed and a drop of five gm/dL in hemoglobin four days after starting rivaroxaban following right femoral popliteal bypass graft stenting. The patient had no liver or kidney abnormalities and was not taking any medication or consuming any foods that could introduce any significant drug interaction. Additionally, we conducted a systematic review of similar reports in the literature with the goal of identifying the factors that could influence rivaroxaban’s levels in the blood or its influence on the INR. We reviewed PubMed using keywords including; “rivaroxaban”, “anti-Xa”, “DOAC”, “elevated”, “INR”, “bleeding”, “hemorrhage”, “pharmacology”, and “pharmacokinetics”. The literature revealed reports of INRs up to 5.2. Reviewing the pharmacokinetics of rivaroxaban indicated possibly higher drug levels in Caucasians, patients with a low body mass index (BMI), and patients with polymorphisms in the genes coding for CYP3A4, CYP2J2, or p-glycoprotein, assuming no renal or liver disease and no significant drug-drug or drug-food interactions. INR can be falsely normal if the thromboplastin reagent used to monitor the INR on warfarin is not sensitive to the changes in INR due to rivaroxaban. We suggest finding a thromboplastin reagent that is sensitive to INR changes with rivaroxaban, which could yield clinically relevant INRs on rivaroxaban allowing for accurate monitoring. We then suggest conducting studies to evaluate the cost effectiveness of regular monitoring in at-risk patients.
Abstract 11972: Economic Burden of Congenital Heart Surgery in China: Results From the National Center for Cardiovascular Diseases
Authors: Qiyu He, Zheng Dou, Shoujun Li
Journal: Circulation (2022)

Introduction: According to Reports on the Prevention and Control of Birth Defects in China, the total lifelong economic burden of new congenital heart diseases (CHD) cases was more than 12.6 billion Chinese Yuan. We aim at exploring the economic burden driven by congenital heart surgery and filling the gap in the health economics in China. Methods: We used data from CDCHS database (Registry No. ChiCTR1800014577) to prospectively analyze the economic burden of congenital heart surgery. The total expenditures were divided into eleven subjects and classified by STAT category, year, and different types of CHD. Stepwise multivariable linear regression model was utilized to analyze the contributing factor to the total expenditure. National economic data was accessed to better describe the burden. Results: A total of 6568 hospitalizations were enrolled from 2018 to 2020. The median of total expenditure of all enrolled patients during hospitalization was 63,129.14 (≈9,910.52 USD), and significant cost-related difference was defined among the five STAT categories (P&lt;0.001) with the lowest in STAT-1 (55,720.43, ≈8,747.46 USD) and highest in STAT-5 (190,587.01, ≈29,919.94 USD). The median total costs during the 3-year 2018 to 2020 period were 57,248.72 (≈8,987.38 USD), 63,423.45 (≈9,956.74 USD) and 67,867.37 (≈10,654.39 USD), respectively. Multivariable linear regression model showed that STAT category, complication, emergent operation and delay sternal closure were the major contributing factor to the total expenditure. Conclusions: For the first time, the economic burden of congenital heart surgery in China is delineated not only in terms of total expenditure but also the detail components. Also, the current healthcare policies in China were analyzed, and combined with the expenditure information, this analysis provides substantial information about specific factors driving to the economic burden with the purpose of aiding policy adjustments.
Abstract 11957: Physical Training Augmented With Whole Body Electronic Muscle Stimulation is Superior to Conventional Training Alone in Healthy Subjects, a Pilot Randomized Controlled Trial
Authors: Jaskanwal D Sara, Nazanin Rajai, Logan Breuer, Jacob Bjerke, Thomas P Olson, Takashi Nagai, Nathan Schilaty, Amir Lerman
Journal: Circulation (2022)

Introduction: Physical activity is protective against cardiovascular (CV) disease and mortality, yet more than 25% of adults do not perform any regular exercise. Whole body electronic muscle stimulation (WB-EMS) is a novel FDA-approved device used for physical training that simultaneously stimulates all major muscle groups using percutaneous electrical impulse transmission during exercise. Preliminary studies demonstrated increased muscle mass, reduced fat mass, and improved functional capacity in elderly individuals who trained with WB-EMS. We evaluated the effects of training with WB-EMS on measures of CV health. Methods: Healthy adults were randomized to physical training with versus without WB-EMS for one 20-minute session each week for 16 weeks. Participants wore a specifically designed vest and arm and leg straps connected to the WB-EMS device (Miha Bodytec, Germany). Biphasic electrical stimulation was delivered through the vest and straps (4 sec on, 4 sec off) at a frequency that elicited a score of 5-6 on the Borg perceived exertion scale when each major muscle group was stimulated. Individuals randomized to no WB-EMS wore the same equipment but received no stimulation. Sessions were provided by trainers certified in WB-EMS training and consisted of a fixed protocol of simple exercises such as squats and lunges. Temporal changes in measures of CV health were compared between groups. Results: Forty-one individuals were recruited between 02/2021 and 02/2022 (n=24 WB-EMS, n=17 no WB-EMS; mean age 35.9±11.2 yrs; 61.3% females; median BMI 24.3 (21.8, 28.1) kg/m 2 . After 16 weeks there were significant and favorable differences in the intervention group compared to controls in waist: hip ratio (-1.2 cm vs. 0.9, p=0.05); total cholesterol (-1.1 mg/kg vs. 14.2 mg/kg, p=0.02); anaerobic threshold (68.2% vs. 30.8%, p=0.03); breathing efficiency (VE/VCO2: -10.36 vs -7.38, p=0.01); and peripheral endothelial function, measured with reactive hyperemia peripheral arterial tonometry (-0.009 vs. -0.29, p=0.06). Conclusions: Once weekly training with WB-EMS yielded more favorable changes in CV biomarkers compared to conventional training alone in healthy adults, and thus may offer an effective and time-efficient method of physical training.
Abstract 12093: Inter-Reader Reliability of Coronary Calcium Estimation From Non-Gated Chest Computed Tomography Scans Using a Semi-Quantitative Scoring Method
Authors: Nehal Dhaduk, Daniel Choi, Samuel Maidman, Dena Hayes, Nathaniel Smilowitz, Robert Donnino
Journal: Circulation (2022)

Introduction: Coronary artery calcium (CAC) is strongly associated with cardiovascular risk. CAC burden can be qualitatively estimated from non-gated chest computed tomography (CT) imaging and may be used to predict future cardiovascular outcomes. We evaluated whether resident physician trainees can reliably estimate CAC burden from existing non-gated chest CTs using a semi-quantitative scoring method. Methods: A group of 4 resident physicians without formal training in CT image interpretation underwent a training session to qualitatively estimate CAC burden from non-gated, contrast and non-contrast CT scans. CAC was estimated for each coronary artery as absent, mild (1-24% vessel length), moderate (25-49% vessel length) and severe (&gt;50% vessel length). All Chest CTs were reviewed by two physicians, each blinded to the interpretations of the other reviewer, to assess (a) the presence or absence of CAC, (b) the presence or absence of moderate-severe CAC, and (c) a semi-quantitative CAC index, at a per-patient level and by vessel. Inter-reader reliability (IRR) was assessed by percent agreement, Cohen's kappa coefficient, and the intraclass correlation coefficient (ICC). Results: Using a semi-quantitative scoring system to estimate an index of overall CAC burden, the ICC was 0.96 (CI 0.94-0.98). The percent agreement for the presence of any CAC was 74% (kappa 0.82) and 89% for moderate-to-severe CAC (kappa 0.85). The IRR stratified for each coronary vessel is shown in Table 1. CAC estimated from both contrast and non-contrast scans was associated with substantial agreement between readers ( Table 1 ). Conclusions: With a single training session, resident physicians can quickly and reliably estimate CAC burden from non-gated chest CT imaging. This may facilitate cardiovascular risk stratification in patients without dedicated cardiac testing. 1b
Abstract 12109: Cardiac LDLR Drives Chimeric SARS-CoV-2-Induced Myocarditis in K18 hACE2tg Mice
Authors: Jose Manuel Condor Capcha, Camila Iansen Irion, Ali Saad, Guerline Lambert, Amanda Wong, Jason Villano, Andrew Pekosz, Mark J Ranek, Lina A Shehadeh
Journal: Circulation (2022)

Introduction: Cardiovascular disease patients with COVID-19 present prolonged hospitalization and increased mortality. Cardiovascular complications including myocarditis have been reported in association with COVID-19. We recently reported that levels of cardiac low-density lipoprotein receptor (LDLR) are elevated in patients with heart failure. We hypothesized that LDLR may play a role in COVID-19-induced myocarditis. Methods: K18 h ACE2 tg mice were inoculated with SARS-CoV-2 Washington (WA-1) native strain, replication-competent chimeric (ch) SARS-CoV-2, or PBS and lung viral load and histopathology were compared (N=4). We interrogated the LDLR in 4-month-old K18 h ACE2 tg mice via intravenous injection of AAV9-cTnT-hLDLR (gain of function), AAV9-cTnT-hIDOL (Induced Degrader of LDLR, loss of function), or AAV9-cTnT-Luciferase (control). After 4 weeks, mice were inoculated intratracheally with chSARS-CoV-2. Five days after inoculation, mice were sacrificed, and blood and tissues collected for histopathological analysis and RNA/protein studies to evaluate myocarditis. Myocarditis was established by histological analysis according to the Dallas criteria. Results: Both native SARS-CoV-2 and chSARS-CoV-2 had ~60% infectivity as measured by qPCR and immunostaining. Over-expression (OE) of cardiomyocyte-specific hLDLR together with chSARS-CoV-2 induced myocarditis with prominent cardiomyocyte degeneration, necrosis, and immune cell infiltration: T cells (59 cells/mm 2 ;p&lt;0.05) and Macrophages (109 cells/mm 2 ;p=0.0002) compared to the single control groups. In addition, hLDLR-OE increased heart expression of Osteopontin (12.6 vs 1.2%;p&lt;0.05), pAKT(Ser473) (14.4 vs 3.5; p&lt;0.05) and ICAM-1 (9.0 vs 3.3%; p&lt;0.05). OE of cardiac-specific hIDOL mice infected with chSARS-CoV-2 reduced macrophage infiltration into the heart compared to hLDLR-OE myocarditis and control chSARS-CoV-2 groups (p&lt;0.0001 and p&lt;0.05), respectively. hIDOL-OE reduced cardiac ICAM-1 compared to myocarditis and control chSARS-CoV-2 groups (p&lt;0.01 and p&lt;0.05), respectively. Conclusions: Cardiac LDLR drives COVID-19-associated myocarditis in a new mouse model of SARS-CoV-2 infection.
Abstract 11861: Reach Out Behavioral Intervention for Hypertension Initiated in the Emergency Department Connecting Multiple Health Systems: A Randomized Control Trial
Authors: Lesli E Skolarus, Mackenzie Dinh, Kelley Kidwell, Chun Chieh Lin, Lorraine Buis, Devin Brown, Rockefeller Oteng, Deborah E Trimble, Candace Whitfield, Zahera Farhan, Adam Flood, Dominic Borgialli, Sacha Montas, William J Meurer
Journal: Circulation (2022)

Introduction: Hypertension (HTN) is the most important modifiable risk factor for cardiovascular disease and disproportionally impacts Black and low-income people. The emergency department (ED) cares for medically underserved populations, many of whom have HTN. Mobile health (mHealth) strategies initiated in safety-net EDs may be one approach to control blood pressure (BP) in a medically underserved population. Hypothesis: A multicomponent, ED initiated multiphase optimization strategy would identify intervention components that reduce BP at 12 months. Methods: Reach Out is a health system focused, health theory based, mHealth 2x2x2 factorial behavioral trial to reduce BP among hypertensive patients evaluated in a safety-net ED. Intervention components included: 1) healthy behavior text messaging (yes vs. no), 2) prompted BP self-monitoring (SMBP) (weekly vs. daily), and 3) facilitated primary care provider (PCP) appointment scheduling and transportation (yes vs. no). The primary outcome was change in systolic BP (SBP) from baseline to 12 months. We fit linear regression models accounting for intervention components, age, sex, race and prior use of BP medications. Results: We randomized 488 participants to the intervention and 211 (43%) participants completed 12-month follow-up. The mean age was 45.5 years, 61% were women, 54% were Black people, 22% did not have a PCP, 10% were uninsured, 21% lacked transportation, 21% did not have a previous diagnosis of HTN and 51% were not taking BP medications. SBP declined in all 8 groups. Overall, across all groups, SBP declined (-9.2 mmHg, 95%CI, -12.2 to -6.3) after 6 months and (-6.6 mmHg, -9.3 to -3.8) after 12 months. In fully adjusted models, no intervention components were associated with a change in systolic BP at 12 months. Conclusions: Higher intensity of the intervention components were not associated with greater reduction in BP. Overall, participants receiving lower intensity levels of our intervention had reductions of BP that were clinically relevant. Future studies should focus on further tailoring intervention components to the needs of participants.
Abstract 12116: Effects of Interleukin-1 Blockade With Anakinra on Peak Oxygen Consumption in Patients With Heart Failure an Analysis of On-Treatment and Off-Treatment Assessments
Authors: Benjamin Van Tassel, Francesco Moroni, Sebastian pinel, Salvatore Carbone, Cory R TRANKLE, Hayley E Billingsley, Azita Talasaz, Michael C Kontos, Charlotte Roberts, Ross A Arena, Justin M Canada, Antonio Abbate
Journal: Circulation (2022)

Introduction: Interleukin-1 (IL-1) blockade may improve exercise capacity in the subset of heart failure (HF) patient with high inflammation. Accordingly, modulating systemic inflammation with IL-1 inhibition could result in physiologic adaptations that have a beneficial effect on exercise capacity in this population. Hypothesis: Primary objective of the study was to determine changes in peak oxygen consumption (VO2) on-treatment with anakinra, an IL-1 blocker, and after treatment cessation. Methods: Cardiopulmonary exercise testing (CPET) was performed in 52 patients with HF at baseline, during daily treatment and after suspension of treatment with 100 mg anakinra. High-sensitivity C-reactive protein (CRP) was measured at the time of each CPET. Data are presented as median and interquartile range or number and percentage. Results: The cohort included twenty-six (50%) females, 36 (69%) self-identified as Black/African-American, 55 [52-62] years. Left ventricular ejection fraction (LVEF) was 43% [34-60%], CRP was 7.1 [3.7-15.8] mg/L and peak VO2 was 14.5 [12.6-17.4] ml•kg-1•min-1. Treatment duration was 4 [2-12] weeks, while time between treatment discontinuation and off-treatment CPET was 12 [6-12] weeks. Treatment with anakinra significantly reduced CRP (7.1 [3.7-15.8] to 1.5 [1.0-3.8] mg/L, p&lt;0.001) and improved peak VO2 (14.5 [12.6-17.4] ml•kg-1•min-1to 16.0 [14.0-18.6] ml•kg-1•min-1, p=0.011-Figures A and B, respectively). CRP significantly increased to 3.8 [1.4-10.7] mg/L, p=0.007, and peak VO2 significantly decreased to 15.5 [12-17.8] ml•kg-1•min-1 (p= 0.004) after anakinra suspension. Conclusions: IL-1 blockade with anakinra is associated with a reduction in systemic inflammation (CRP levels) and in an improvement in exercise capacity (i.e., peak VO2) among patients with HF during treatment. These data validate IL-1 blockade as a mediator of exercise capacity in HF; however long-term effects require further investigation.
Abstract 11725: Exosomes Secreted from TSG6-Rich Adipose-Derived Stem Cells Induce Neovascularization in Ischemic Limb
Authors: Kosei Yamaguchi, Oto Inoue, Soichiro Usui, Ayano Nomura, Daiki Hashimuko, Yusuke Takeda, Chiaki Goten, Shinichiro Takashima, Kenji Sakata, Kenji Iino, Hirofumi Takemura, Masayuki Takamura
Journal: Circulation (2022)

Introduction: Therapeutic angiogenesis is attractive for tackling cardiovascular disease. Exosomes, which contain growth factors and micro RNAs, might be useful to develop cell-free therapeutic angiogenesis. Previously we have reported that CD271+ADRCs have excellent angiogenic activity. In this study, we investigated the in vivo angiogenic effects and mechanisms of CD271+ ADSC-derived exosomes (CD271+ Exo) using a mouse model of limb ischemia. Methods: We analyzed single-cell RNA-sequencing data of human stromal vascular fraction (SVF) cells. After normalization and clustering, CD271+ and CD271- cells were analyzed in DESeq2. Next, we established CD271+/- ADSCs from human SVF using FACS. After 48 hours of serum deprivation, conditioned media was collected. Exosomes were purified by magnetic isolation using phosphatidylserine/Tim4 interaction and confirmed by ELISA of exosomal markers. We labeled exosomes by PKH26 membrane dye and injected them into a mice model of limb ischemia. After 2 weeks, lectin perfused limb was harvested and analyzed by immunohistochemistry (Fig.A). Results: In single-cell transcriptome of human SVF, TSG6 was predominantly expressed in Lineage-CD34+ stromal cells. Furthermore, TSG6 was significantly upregulated in CD271+ SVF cells compared to CD271- SVF cells and other cluster cells (Fig.B). Consistently, TSG6 mRNA expression was upregulated in CD271+ ADSCs (Fig.C). We confirmed exosomal marker expression (CD63, CD9, and CD81) of isolated Exo (Fig.D). In exosome therapy, CD271+ Exo promotes neovascularization compared to CD271- Exo or PBS. Notably, there were more cells containing PKH labeling in the CD271+ Exo-treated group (Fig.E). Conclusions: This study reveals a novel mechanism by which CD271+ Exo promotes angiogenesis via TSG6. CD271+ Exo would be useful for cell-free therapeutic angiogenesis.